The present invention relates to improved methods for detecting tumors in the course of intraoperative and endoscopic examination using a small radiation detecting probe, whereby background radiation is reduced, or compensated for, and discrimination between tumor and non-tumor tissue is thereby enhanced.
Surgical resection remains the primary curative approach in the management of cancer. Radioimmunodetection (RAID) is used to locate and stage tumors, and to monitor post-operative patients, typically using serum levels of markers (antigens) produced by and/or associated with tumors ("tumor markers"), e.g., carcinembryonic antigen (CEA), as both a pre-operative diagnostic predicate and a post-operative diagnostic indicator of recurrence. Antibodies and/or antibody fragments which specifically bind tumor markers ("anti-cancer antibodies") are used as carriers for radiolabels in imaging and for in vitro assays. It will be appreciated that a tumor antigen can serve as a target for an antibody carrier even if it is not present in serum in a detectable amount.
Resolution is affected by several factors that can limit the size of a tumor, especially a metastasis, which can be imaged by RAID. Non-invasive RAID is inherently limited by the distance between the radiation detector and the tumor. In the case of small, deep-seated metastatic tumors, this becomes the limiting factor in their detection.
Second look surgery has been practiced where recurrence of a previously excised primary tumor was indicated by elevated levels of tumor marker, e.g., CEA. Recently, a small gamma detection probe has been developed which is capable of detecting gamma emission at short distances. Its intraoperative use in second look surgery has been reported to provide important information to the surgeon for determining safe margins for resection and for detecting small metastases, by Aitken et al., Dis. Colon & Rectum, 27, 279-282(1984).
Nevertheless, elevated background radiation levels can interfere with and vitiate the advantage of short measuring distances in this technique. In addition, non-specific immunoglobulin uptake by tumor tissue can complicate diagnosis. Moreover, background radiation due to non-specific uptake of labeled antibody often increases with time after injection thereof and clearance of non-specific background radioactivity can require several days for optimal detection of tumors. A need therefore continues to exist for methods for reducing background levels and compensating for non-specific immunoglobulin uptake so that enhanced resolution can be achieved for short-range intraoperative and endoscopic tumor detection and therapy.